“It takes a village,” said NYU Winthrop researcher Allison Reiss, MD, as she and her team gathered recently to celebrate receiving a Grant-in-Aid from the American Heart Association (AHA). The grant, titled, “Methotrexate and Cholesterol Transport Regulation: Impact of Treatment Regimen in Diabetes and Metabolic Syndrome,” poses the question: “Will reducing inflam- mation prevent a second heart attack?” and is designed to assess the impact of low dose methotrexate (a widely used anti-inflamma- tory therapy for rheumatoid arthritis (RA)) on cholesterol transport in the body. Dr. Reiss is the Principal Investigator, with co- investigators Alan Jacobson, MD, Chief Research Officer at NYU Winthrop; Joshua De Leon, MD, Director of the Cardiovascular Training Program, Director of Nuclear Cardiology and Director of Cardiovascular Research; and Steven Carsons, MD, Chief of the Division of Rheumatology, Allergy and Immunology.

“We have an amazing team effort and approach here at NYU Winthrop and we couldn’t have achieved this honor without each indi- vidual,” said Dr. Reiss, crediting the research associates, technicians, coordinators and everyone who also helped make the grant possible (see sidebar).

“This is a potential game-changer in the way we treat heart attacks, especially those in people with diabetes or at a high risk for diabetes because of metabolic syndrome,” said Dr. Jacobson. Dr. Jacobson describes Dr. Reiss’s work as “invaluable.” “It really plays into the potential underlying mechanisms of why this drug – methotrexate – might work and goes to the core of the underlying biological mechanism of the study,” he said.

The grant builds on the work Dr. Reiss and her team at NYU Winthrop began in 2014 as part of a major study funded by the National Institutes of Health (NIH) called the Cardiovascular Inflammation Reduction Trial (CIRT), which had a similar goal to that of the recent grant. Through this study, Dr. Reiss and her team have been investigating whether taking low dose methotrexate reduces cardiovascular events in individuals with type 2 diabetes or metabolic syndrome who have had a heart attack or multiple coronary blockages. The recent grant awarded to the team signals the start of a sub-study that will be even more in-depth, making NYU Winthrop an “independent and innovating contribu- tor to the science,” according to Dr. Reiss.

“It gives us the opportunity to answer the ‘why,’ ‘how,’ and ‘what’ is happening in the blood in regards to methotrexate that is protecting patients,” said Dr. Reiss. “Through this research, we can determine how patients can be best treated and how people handle the drug.”

Dr. De Leon is the leader of the clinical aspect of the project, identifying cardiology patients for the trial, and Dr. Carsons lends an immunological perspective from his experience as a rheumatologist who works with methotrexate in his arthritis patients.

“One of NYU Winthrop’s strengths rests in its ability to bridge the laboratory and the bedside,” said Dr. De Leon. “This group has been so innovative in generating new knowl- edge and discovering the role of inflammation in altering how the cell handles cholesterol at the basic level, and how inflammation worsens atherothrombosis (the hardening and narrowing of the body’s arteries). This grant is the next step in translating all these years of basic research to patient care.”

“Our team’s unique ability to study the molecular interface between inflammation in the body and the development of heart disease has led to this important approach to cardiovascular disease prevention,” said Dr. Carsons. The results of this study have the potential to open up new ways to treat car- diovascular disease and come up with a mechanism to identify patients who will respond best to the treatment.

Dr. Reiss (second from left) gathers with her team to celebrate the American Heart Association grant.

“It means so much to be funded by the American Heart Association, a prestigious and renowned organization that has made so many contributions to allocating funds for heart disease and preventing heart attacks,” said Dr. Reiss. “We are looking forward to honoring this incredible award and doing this work to make a substantial contribution to medical knowledge of patient care.”